Mutations of epithelial growth factor receptor (EGFR) in exon 19 and 21 are both believed to be associated with carcinogenesis, sensitivity to tyrosine kinase drugs and with the prognosis of non-small cell lung cancers (NSCLCs). However, their exact clinical significance remains disputable. We detected the mutations of 157 NSCLCs from mainland China with high resolution melting analysis and identified exon mutations with DNA sequencing. Of the 157 cases examined, 57 displayed EGFR mutations which included 22 in exon 19 and 35 in exon 21. Current research has shown that EGFR mutations are more commonly associated with the female population and East Asians, with additional significance being adenocarcinomas. Our current findings are supporting this sugestion. We analysed the clinicalpathological characteristics of mutations in exon 19 and 21 separately, which showed that the mutation frequency of NSCLCs in exon 21, but not in exon 19, were significantly higher in females. Comparatively, mutation frequencies in exon 19 were significantly higher in the stage I and II than in the stage III abnd IV, while tumors with lymph node metastasis and the stage III and IV demonstrated significantly higher mutation frequencies in exon 21. Additionally, exon mutations in the left and right lung showed significant differences: with exon 19 mutations being more frequent in the tumors of left lung, and exon 21 mutuations showing a higher incidence in right lung tumors. This suggests that, in mainland China, NSCLCs with EGFR mutations in exon 19 could have a less malignant character than those with mutations in exon 21. It's the first report that EGFR mutations in exon 19 and exon 21 in NSCLC patients may relate to the tumor sites, but further research is still required.

Compared with the platinum-based doublets chemotherapy, EGFR-TKI significantly prolonged PFS, increased ORR, improved qol, not significantly increased the nonhematologic toxicity and at the same time decreased the nonhematologic toxicity but not significantly increased the transaminase toxicity for advanced NSCLC patients in East Asia. Although there is convincing evidence to confirm the results mentioned herein, they still need to be confirmed by large-sample trials.

Background Meloxicam is a selective cyclooxygenase-2 inhibitor used for pain relief, but its poor solubility limits its clinical applications. QP001 is a novel intravenous formulation of meloxicam developed with PEG and pH regulator to improve its solubility. This study aimed to evaluate the safety, tolerability, and pharmacokinetics of QP001 in Chinese healthy subjects. Methods The trial consisted of three parts. Part I was a two-period crossover study to evaluate bioavailability, in which 10 healthy were either intravenously infused with 15mg QP001 (test) or orally given 15mg Mobic Ⓡ (reference). Part II was a single-arm design to assess the pharmacokinetic (PK) characteristics after 30 mg single- and multiple-dose QP001 in 10 subjects. In part III, we investigated the PKs and tolerability of QP001 at a high dose (60 mg) in another 10 subjects. The PK parameters and treatment-emergent adverse events (TEAEs) were evaluated. Results A total of 30 subjects were enrolled in the study. QP001 was well tolerated and safe without significant TEAEs in all three study parts. The PK characteristics of QP001 were linear following a single-dose range of 15–60 mg (C max and AUC 0-t were 5.82–17.66 μg/mL and 58.08–251.17 μg∙h/mL, respectively). After five consecutive daily 30 mg doses, the accumulation index was around 1.98, which indicated a minimal accumulation of QP001. Compared to the tablet dosage form, the relative bioavailability of QP001 reached 116.85%. Additionally, the PK profile of QP001 showed no gender difference. Conclusion QP001 was well tolerated in healthy Chinese subjects after single ascending doses up to 60 mg and multiple-dose of 30 mg. Based on the PK and safety results, QP001 is a promising once-daily intravenous COX-2 inhibitor candidate for managing pain. Trial Registration The trial is registered at chinadrugtrials.org.cn (ChiCTR2100047884).